S-Adenosylmethionine (AdoMet) is a key compound in amino acid metabolism, and in the regulation of many biological processes which includes transmethylation, transsulfuration, and polyamine biosynthesis. The primary goal of this project is to study the synthesis and metabolism of AdoMet in normal and cataractous lenses. Lenticular methionine adenosyltransferase (MAT), the enzyme which synthesizes AdoMet has been partially purified from rat lens, and its properties studied (Geller et al.). In contrast to previous reports, we were able to show that the lenticular MAT is distinctly different from the major high Km isozyme normally found in liver, and is very similar to the highly purified MAT from human lymphocytes. Further purification of the enzyme and more detailed kinetic studies will be conducted. Preliminary studies show that lens MAT is inhibited by each of its endproducts, Pi, PPi, and AdoMet, and a combination of Pi and PPi are strongly inhibitory. Studies will be carried out to determine the physiological significance of this mode of inhibition. Like the human lymphocyte enzyme and the low Km isozyme from rat liver, lenticular MAT is inhibited by DMSO. Since DMSO is a cataractous agent, its effect on MAT and AdoMet synthesis will be studied. Cultured lenses will be used to study AdoMet synthesis and turnover. MAT activity and AdoMet levels will be studied in animals of different ages. The long term goals of this project will be to study the role and metabolism of AdoMet in lenses. The concentration of the AdoMet metabolites, S-adenosylhomocysteine and decarboxylated AdoMet, will be measured, and the synthesis of polyamines from ornithine and decarboxylated AdoMet will be studied. World-wide, cataracts are a major cause of blindness. In senile cataracts, metabolic changes which involve the sulfur amino acids, methionine and cysteine, are observed. These studies should help us develop a greater understanding of the control of methionine metabolism in normal lenses, with the expectation that this will shed light on the etiology of cataracts.